Angelica sinensis polysaccharide inhibits pyroptosis and improves osteoarthritis through the collaborative power of PPARγ and Nrf2.

BACKGROUND AND AIM: Osteoarthritis (OA) is an inflammatory disease, and pyroptosis causes a local inflammatory microenvironment that leads to chondrocyte disorder. This article aims to show that angelica sinensis polysaccharide (ASP) can improve the antioxidant and anti-inflammatory capacity of chondrocytes through the collaborative power of PPARγ and Nrf2, downregulate pyroptosis, and thus alleviate OA. METHODS: After analyzing the clinical samples, the therapeutic effect of ASP was assessed in vitro and in vivo, respectively. The concentrations of lipopolysaccharide (LPS) with ATP were determined by CCK-8. Pyroptosis was evaluated by lactate dehydrogenase (LDH) release, caspase-1 staining, cell viability and cytotoxicity, mitochondrial membrane potential (MMP) detection, and measurement of ROS. The expression of PPARγ, Nrf2, NLRP3, ASC, caspase-1, GSDMD-N, NF-κB, SOD2, and Cyt-C was detected by qRT-PCR, Western blot, immunofluorescence, and immunohistochemistry. RESULTS: The expression of the NLRP3 inflammasome in OA cartilage was increased, and inflammatory cytokines were higher in OA serum. LPS promoted oxidative stress and induced pyroptosis in chondrocytes, while ASP mediated the collaborative power of PPARγ and Nrf2 to improve the viability of chondrocytes, reduce the activity of the NLRP3 inflammasome, and inhibit pyroptosis. CONCLUSION: These findings revealed the process of pyroptosis in chondrocytes and the enhancement of PPARγ and Nrf2 by ASP, which deepens our understanding of OA pathogenesis and could provide new insights for treatment.